Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Neoplastic Cells, Circulating

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Vinorelbine

Mitogens

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by fluorescence in situ hybridization (FISH) (mean ratio \> 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.

Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio \> 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.

trastuzumab

vinorelbine

Ian Krop, MD, PhD

The purpose of this research study is to see what effects trastuzumab in combination with vinorelbine has on breast cancer when the participant has circulating tumor cells that are positive for the protein called HER2. Trastuzumab is an FDA approved drug that targets HER2. The drug combination of trastuzumab and vinorelbine is an effective treatment for patients with breast cancers that are positive for HER2. This trial seeks to determine if the combination can also benefit participants whose original breast cancer was HER2 negative but whose circulating tumor cells are HER2 positive.

OBJECTIVES:

Primary

* To assess the objective response rate (ORR) of trastuzumab and vinorelbine in patients with metastatic breast cancer with HER2 negative primary tumors and HER2 positive circulating tumor cells.

Secondary

* To describe the number of CTCs and the CTCs characteristics before and after therapy, and to explore the correlation of these findings with response.
* To further characterize the safety and tolerability.
* To evaluate progression-free survival.
* To evaluate clinical benefit rate \[complete response (CR)+partial response (PR)+stable disease (SD)\>24 weeks\].

Exploratory

* To determine the clinical feasibility of high-throughput mutation profiling on circulating tumor cells (CTCs).

The analysis was performed for 2 separate cohorts due to a change in study conduct during the trial (see arm description).

Trastuzumab and Vinorelbine in Advanced Breast Cancer

A Phase II, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With Human Epidermal Growth Factor-2 (HER2) Negative Primary Tumors and HER2 Positive Circulating Tumor Cells

ORR was defined as the percentage of patients achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

CBR was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration

PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

CTCs levels were determined based on established methods.

Brigham and Women's Hospital

Beth Israel Deaconess Medical Center

Massachusetts General Hospital

Genentech, Inc.

Dana-Farber Cancer Institute

Assistant Professor of Medicine

Based on common terminology criteria for adverse events version 4(CTCAEv4), maximum grade toxicity by type was first calculated for AEs with trastuzumab and/or vinorelbine treatment-attribution of possibly, probably or definite. Grade 3 or higher AEs were classified as serious and grade 1-2 AEs were classified as other. No further data is available to specify classification of other beyond the general term.

Trastuzumab and Vinorelbine - Cohort A

Trastuzumab and Vinorelbine - Main Cohort

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Positive

Negative

Unknown

Estrogen Receptor Status at Metastatic Diagnosis

Progesterone Receptor Status at Metastatic Diagnosis

The analysis dataset is comprised of all treated patients.

The study terminated early due to insufficient response per statistical design.

Objective Response Rate (ORR)

Clinical Benefit Rate (CBR)

Progression-Free Survival (PFS)

The CTCs in cohort A were analyzed using a non-CLIA approved assay and thus it was felt that the outcome data for this cohort were not evaluable. A new CLIA approved assay was used for the main cohort.

Spots Global Cancer Trial Database for Trastuzumab and Vinorelbine in Advanced Breast Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial